Diverse functional consequences of mutations in the Na+/K+-ATPase alpha2-subunit causing familial hemiplegic migraine type 2.

The Journal of Biological Chemistry
Neslihan N TavrazMartin Dichgans

Abstract

Mutations in ATP1A2, the gene coding for the Na(+)/K(+)-ATPase alpha(2)-subunit, are associated with both familial hemiplegic migraine and sporadic cases of hemiplegic migraine. In this study, we examined the functional properties of 11 ATP1A2 mutations associated with familial or sporadic hemiplegic migraine, including missense mutations (T263M, T376M, R383H, A606T, R763H, M829R, R834Q, R937P, and X1021R), a deletion mutant (del(K935-S940)ins(I)), and a frameshift mutation (S966fs). According to the Na(+)/K(+)-ATPase crystal structure, a subset of the mutated residues (Ala(606), Arg(763), Met(829), and Arg(834)) is involved in important interdomain H-bond networks, and the C terminus of the enzyme, which is elongated by the X1021R mutation, has been implicated in voltage dependence and formation of a third Na(+)-binding site. Upon heterologous expression in Xenopus oocytes, the analysis of electrogenic transport properties, Rb(+) uptake, and protein expression revealed pronounced and markedly diverse functional alterations in all ATP1A2 mutants. Abnormalities included a complete loss of function (T376M), impaired plasma membrane expression (del(K935-S940)ins(I) and S966fs), and altered apparent affinities for extracellular cat...Continue Reading

References

Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·A G WattsR Levenson
Oct 16, 1986·Nature·M Nakao, D C Gadsby
Mar 7, 1998·Journal of Molecular Evolution·K B Axelsen, M G Palmgren
Apr 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·N HadjikhaniM A Moskowitz
Jun 13, 2001·Biochemical and Biophysical Research Communications·E J Kamsteeg, P M Deen
Jul 7, 2001·The New England Journal of Medicine·A DucrosE Tournier-Lasserve
Jan 5, 2002·Journal of Bioenergetics and Biomembranes·P L JorgensenP A Pedersen
Jun 5, 2002·Annual Review of Biochemistry·Jack H Kaplan
Aug 9, 2002·Nature·Chikashi Toyoshima, Hiromi Nomura
Oct 22, 2002·American Journal of Physiology. Cell Physiology·Vera A GolovinaMordecai P Blaustein
Nov 30, 2002·The Journal of Biological Chemistry·Amy E MoseleyJerry B Lingrel
Dec 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Haruo Ogawa, Chikashi Toyoshima
Jan 14, 2003·Annual Review of Physiology·Peter L JorgensenSteven J D Karlish
May 3, 2003·Nature Reviews. Neuroscience·Daniela Pietrobon, Jörg Striessnig
Oct 9, 2003·The Journal of Biological Chemistry·Jan B KoenderinkThomas Friedrich
Nov 26, 2003·Lancet Neurology·Kaate R J VanmolkotMichel D Ferrari
Feb 3, 2004·Annals of Neurology·Michael A MoskowitzTurgay Dalkara
Jun 3, 2004·Annals of Neurology·Kathryn J SwobodaSotiris Youroukos
Jun 4, 2004·Nihon rinsho. Japanese journal of clinical medicine·Miho Iigaya, Norihiro Suzuki
Apr 22, 2005·Biochimica Et Biophysica Acta·Jan B KoenderinkThomas Friedrich
Jul 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Laura SegallRhoda Blostein
Aug 10, 2005·Human Mutation·Florence RiantElisabeth Tournier-Lasserve
Jan 27, 2006·Annals of Neurology·K R J VanmolkotA M J M van den Maagdenberg
Feb 14, 2006·Cephalalgia : an International Journal of Headache·F PierelliF M Santorelli
Mar 16, 2006·European Journal of Human Genetics : EJHG·Kaate R J VanmolkotArn M J M van den Maagdenberg
Dec 5, 2006·Brain : a Journal of Neurology·L L ThomsenJ Olesen
Dec 14, 2007·Nature·J Preben MorthPoul Nissen
Jan 1, 1967·Annual Review of Biochemistry·R W Albers

❮ Previous
Next ❯

Citations

Apr 27, 2011·Molecular Genetics and Genomics : MGG·Bridget H Maher, Lyn R Griffiths
Dec 24, 2010·Nature Reviews. Molecular Cell Biology·J Preben MorthPoul Nissen
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Siddhartha YaragatupalliPablo Artigas
Oct 27, 2011·The Journal of Biological Chemistry·Einat Kapri-PardesSteven J D Karlish
Nov 26, 2011·The Journal of Biological Chemistry·Vivien Rodacker SchackBente Vilsen
Jun 16, 2010·The Journal of General Physiology·Natascia Vedovato, David C Gadsby
Oct 30, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·J Preben MorthPoul Nissen
May 21, 2009·Human Genetics·Boukje de VriesArn M J M van den Maagdenberg
Jul 12, 2014·Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz·T Freilinger
Jan 21, 2014·Cellular and Molecular Life Sciences : CMLS·Marisa BriniErnesto Carafoli
Nov 30, 2012·Annual Review of Physiology·Daniela Pietrobon, Michael A Moskowitz
Sep 4, 2012·The Journal of Headache and Pain·Cherubino Di LorenzoFilippo M Santorelli
Jul 26, 2016·Frontiers in Physiology·Thomas FriedrichCornelia Junghans
Jun 19, 2014·Biophysical Journal·Travis J MitchellPablo Artigas
Apr 27, 2013·Revue neurologique·A Ducros
Dec 8, 2016·Biophysical Journal·Kevin S StanleyPablo Artigas
Jul 11, 2013·Cephalalgia : an International Journal of Headache·Tiziana PisanoDario Pruna
May 8, 2016·Cephalalgia : an International Journal of Headache·Shih-Pin ChenKatharina Eikermann-Haerter
May 15, 2013·Cephalalgia : an International Journal of Headache·Else EisingArn M J M van den Maagdenberg
Oct 17, 2017·The Journal of General Physiology·Dylan J MeyerPablo Artigas
Mar 1, 2018·Cephalalgia : an International Journal of Headache·Marjo Eveliina HiekkalaMikko Kallela
Jun 30, 2016·EMBO Molecular Medicine·Clizia CapuaniDaniela Pietrobon
Feb 6, 2014·Molecular Genetics & Genomic Medicine·Oriel CarreñoBru Cormand
Feb 10, 2017·Physiological Reviews·Peter J GoadsbySimon Akerman
May 17, 2019·Current Neuropharmacology·Anisa Dehghani, Hulya Karatas
May 30, 2009·Annals of Neurology·Andrew Charles
Mar 20, 2015·Pain·Else A TolnerArn M J M van den Maagdenberg
Jun 7, 2020·The Journal of Headache and Pain·Irene de BoerArn M J M van den Maagdenberg
Jun 23, 2019·The Journal of Headache and Pain·Heidi G SutherlandLyn R Griffiths
Mar 20, 2009·Lancet Neurology·Douglas E Crompton, Samuel F Berkovic

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Laura SegallRhoda Blostein
European Journal of Human Genetics : EJHG
Kaate R J VanmolkotArn M J M van den Maagdenberg
Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Daniela Pietrobon
© 2022 Meta ULC. All rights reserved